1. Field of the Invention
The field of this invention is delivery of agents to breast milk ducts.
2. Description of the Background Art
Drug delivery to breast cancer patients, and patients having other breast conditions requiring therapeutic intervention, has been limited to systemic administration of the prescribed drug, the clear disadvantage of which is that the whole body is treated for a condition localized in the breast. Although systemic antibiotics for mastitis (infection in the breast duct) are reasonable treatments, and where the breast cancer has become metastatic, systemic administration is also reasonable, there are conditions that remain confined to the breast tissue and which would be most effectively treated by local administration.
Local surgical intervention is common in the treatment of localized breast cancer, as evidenced by the widespread practice of fine needle biopsies (FNAs), lumpectomy (breast lump removal), and partial mastectomy. Often following a lumpectomy or partial mastectomy, the breast tissue is radiated adjunctively. Such procedures generally disrupt the breast tissue, and in any event do not provide an opportunity for local delivery of a therapeutic agent to the breast.
Diagnostic procedures are being developed which involve collecting ductal fluid, in some cases by cannulating or catheterizing a breast duct to collect such fluid for cytological or marker analysis. Originally, retrieval of ductal fluid was facilitated by collecting the fluid from spontaneous nipple discharge, and later from nipple aspiration. Papanicolaou et al., (1958) Cancer, 11:377-409 describes exfoliative cytology from spontaneous nipple discharge of the human mammary gland and its value in the diagnosis of breast cancer. Goodson W H & King E B, Chapter 4: Discharges and Secretions of the Nipple, The Breast: Comprehensive Management of Benign and Malignant Diseases (1998) 2nd Ed. Vol 2, Bland & Kirby Eds. W. B. Saunders Co, Philadelphia, Pa. pp. 51-74 describes nipple discharge and the ways in which it has been used to characterized conditions of the breast. Nipple aspirate cytology for the study of breast cancer precursors is described in King et al., (1983) Journal of the National Cancer Institute 71(6): 1115-21. Cytological epithelial hyperplasia and a typical hyperplasia diagnosed in nipple aspirate fluid are associated with increased risk of breast cancer in a study of 2701 women as described in Wrensch et al., (1992) Am. J Epidemiology, v. 135 (2): 130-141. Nipple aspirate fluid is identified as a promising non-invasive method to identify cellular markers of breast cancer risk in Sauter et al., (1997) British Journal of Cancer 76(4): 494-501.
Diagnosis using ductal fluid retrieved by accessing the duct with a lumen-based device such as a catheter or cannula is described by Sartorius et al., (1977) which proposed cytologic evaluation of breast fluid retrieved using hair-like single-lumen catheters for the detection of breast disease as described in Journal of the National Cancer Institute 59(4): 1073-80. Love and Barsky, (1996) Lancet 348(9033): 997-9 demonstrated retrieval of ductal fluid by breast-duct endoscopy using a single-lumen device to study stages of cancerous breast disease.
A company called Diagnostics, Inc. formed in 1968, produced devices to obtain breast ductal fluid for cytological evaluation. The devices included a nipple aspiration device to collect NAF from subjects, and single-lumen catheters to retrieve ductal fluid. The devices were sold prior to May 28, 1976, for the purpose of collecting breast ductal fluid for cytological evaluation.
Co-owned and copending U.S. patent application Ser. Nos. 09/067,661, filed Apr. 28, 1998, and Ser. No. 09/301,058 filed Apr. 28, 1999, and a corresponding PCT filed case describe and claim methods of ductal lavage using dual lumen catheters for infusing wash fluid through the infusion lumen and retrieving ductal fluid that mixes with the wash fluid and that is collected through a collection lumen of a dual lumen catheter. Co-owned and copending U.S. patent application No. 60/143,359 filed Jul. 12, 1999, describes and claims a dual lumen catheter for delivery and retrieval of ductal fluid for diagnosis. Co-owned and copending U.S. patent application No. 60/122,076 filed Mar. 1, 1999, (manifold) describes and claims a manifold device for lumen-based delivery of a therapeutic agent to multiple breast ducts on a single breast at the same time.
While cannulation and catheterization are suitable means for diagnostic retrieval of breast duct fluid, and also reasonable approaches to intraductal delivery of therapeutic agents, it would be a great advantage to improve upon the intraductal delivery devices and modalities available to patients having localized breast conditions for which the safest, least toxic and most effective therapeutic administration is intraductal.
The present invention improves upon existing and developing intraductal therapy by providing alternative intraductal delivery devices and modalities, and by extending the usefulness and practice of the presently known and described intraductal delivery modalities using ductal catheterization and ductal cannulation.
Relevant Literature
U.S. Pat. No. 5,763,415, to Sukumar discloses prophylactic and therapeutic methods of treating the ductal epithelium of a breast duct by treating the duct with an epithelium destroying agent, and claims a method of treating the ductal epithelium of a mammary gland prophylactically or therapeutically for cancer by ductal cannulation of a duct, and administration of a vector comprising thymidine kinase to the duct and its prodrug ganciclovir.
U.S. Pat. No. 4,981,692, to Popescu et al., discloses and claims a method of treating infections in an animal (particularly bovine animals) by administration of a therapeutically effective amount of aminoglycoside in liposome form by intramammary infusion.
U.S. Pat. Nos. 4,202,329 and 4,365,632, to Kortum disclose a process and apparatus for stimulating immune resistance by the introduction of at least one relatively small solid non-toxic substantially non-biodegradable body, having non-specific antigenic action, into each gland cistern of the udder. The continued presence of the non-specific antigenic body induces immune resistance including an increase in the number and activity of phagocytic cells in the udder, which in turn provides protection against bacterial invasion without degrading milk quality. U.S. Pat. No. 4,202,329 claims a method for inhibiting bacterial infection by use of this process and apparatus.